Non-Coding RNAPub Date : 2025-05-16DOI: 10.3390/ncrna11030040
Verena Schlösser, Helen Louise Lightfoot, Christine Leemann, Seyedeh Elnaz Banijamali, Aathma Merin Bejoy, Shashank Tiwari, Jeffrey L Schloßhauer, Valentina Vongrad, Andreas Brunschweiger, Jonathan Hall, Karin J Metzner, Jochen Imig
{"title":"Correction: Schlösser et al. Anti-HIV-1 Effect of the Fluoroquinolone Enoxacin and Modulation of Pro-Viral hsa-miR-132 Processing in CEM-SS Cells. <i>Non-Coding RNA</i> 2025, <i>11</i>, 8.","authors":"Verena Schlösser, Helen Louise Lightfoot, Christine Leemann, Seyedeh Elnaz Banijamali, Aathma Merin Bejoy, Shashank Tiwari, Jeffrey L Schloßhauer, Valentina Vongrad, Andreas Brunschweiger, Jonathan Hall, Karin J Metzner, Jochen Imig","doi":"10.3390/ncrna11030040","DOIUrl":"10.3390/ncrna11030040","url":null,"abstract":"<p><p>Seyedeh Elnaz Banijamali was not included as an author in the original publication [...].</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Non-Coding RNAPub Date : 2025-05-14DOI: 10.3390/ncrna11030039
Olga R Borodulina, Sergey A Kosushkin, Ilia G Ustyantsev, Nikita S Vassetzky, Dmitri A Kramerov
{"title":"Analysis of RNA Transcribed by RNA Polymerase III from B2 SINEs in Mouse Cells.","authors":"Olga R Borodulina, Sergey A Kosushkin, Ilia G Ustyantsev, Nikita S Vassetzky, Dmitri A Kramerov","doi":"10.3390/ncrna11030039","DOIUrl":"10.3390/ncrna11030039","url":null,"abstract":"<p><p><b>Background/Objectives:</b> SINEs (short interspersed elements) are eukaryotic non-autonomous retrotransposons. They are transcribed by RNA polymerase III (pol III) and generate non-coding RNAs. The 3' end of many mammalian SINEs contains a polyadenylation signal (AATAAA), a pol III transcription terminator, and an A-rich tail. Studies have shown that, in human HeLa cells that have been transiently transfected with such SINEs, short pol III-generated SINE transcripts undergo polyadenylation, resulting in the addition of a long poly(A)-tail. Notably, this AAUAAA-dependent polyadenylation is not characteristic of any other transcripts synthesized by pol III. B2 SINEs, found in the genomes of mouse-like rodents, exemplify all these features. <b>Methods:</b> In this study, we implemented a novel approach to sequencing pol III-generated B2 transcripts from mouse cell cultures (L929 and 4T1) and organs (brain and testis). <b>Results:</b> Transcription occurred in 16,000-20,000 B2 copies in each cell type, 51-62% of which were transcribed in all four cell types. Effective transcription terminators (e.g., TCT<sub>>3</sub> and T<sub>≥4</sub>) were found in approximately 40% of the transcribed B2 copies. The transcripts of these B2 copies contained a truncated terminator sequence, as pol III transcriptional arrest is known to occur within the terminator, with a poly(A)-tail immediately downstream. Such a tail could only have formed through RNA polyadenylation. <b>Conclusions:</b> These results demonstrate that B2 transcripts synthesized by pol III are capable of polyadenylation in mouse cells. We discuss the transcription of B2 copies with and without moderately efficient pol III terminators (TCTTT) and provide examples of the polyadenylation of such transcripts.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Small RNA Landscape of Platelet Dust: Platelet-Derived Extracellular Vesicles from Patients with Non-Small-Cell Lung Cancer.","authors":"Mafalda Antunes-Ferreira, Ilias Glogovitis, Diogo Fortunato, Silvia D'Ambrosi, Mariona Colom Saborit, Galina Yahubyan, Vesselin Baev, Michael Hackenberg, Natasa Zarovni, Thomas Wurdinger, Danijela Koppers-Lalic","doi":"10.3390/ncrna11030038","DOIUrl":"10.3390/ncrna11030038","url":null,"abstract":"<p><p><b>Background:</b> Platelet-derived Extracellular Vesicles, or \"Platelet Dust\" (PD), are reported as the most-abundant extracellular vesicles in plasma. However, the PD molecular content, especially the small RNA profile, is still poorly characterized. This study aims to characterize PD and other extracellular vesicles (EVs) in patients with non-small-cell lung cancer (NSCLC), focusing on their small RNA signatures and diagnostic potential. <b>Methods:</b> The EVs were isolated directly from the plasma of healthy donors and patients with NSCLC using the surface markers CD9, CD63, CD81 (overall EVs), and CD61 (PD). Small RNA sequencing was then performed to comprehensively profile the miRNAs. <b>Results:</b> Our analysis revealed distinct small RNA profiles in the EVs and the PD from the patients with NSCLC. The EVs (CD9-, CD63-, and CD81-positive) showed the enrichment of four miRNAs and the depletion of ten miRNAs, while the PD (CD61-positive) exhibited a more complex profile, with nineteen miRNAs enriched and nine miRNAs depleted in the patients with NSCLC compared to those of the healthy controls. <b>Conclusions:</b> This exploratory study enhances our understanding of miRNA composition within different plasma vesicle populations, shedding light on the biology of plasma vesicles and their contents. Furthermore, utilizing an extracellular vesicle isolation method with potential clinical applicability offers the prospect of improved cancer characterization and detection by selecting the most informative subpopulation of plasma vesicles.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Non-Coding RNAPub Date : 2025-05-06DOI: 10.3390/ncrna11030037
Montiel Guerrero-Sabater, María Cosín-Villanueva, Pedro Almiñana-Pastor, Andrés López-Roldán
{"title":"Expression of miRNAs in the Relationship Between Periodontitis and Cardiovascular Diseases: A Systematic Review.","authors":"Montiel Guerrero-Sabater, María Cosín-Villanueva, Pedro Almiñana-Pastor, Andrés López-Roldán","doi":"10.3390/ncrna11030037","DOIUrl":"10.3390/ncrna11030037","url":null,"abstract":"<p><strong>Objectives: </strong>Periodontitis is a chronic inflammatory disease that could influence the pathophysiology of cardiovascular diseases through immunoinflammatory and epigenetic mechanisms. MicroRNAs (miRNAs) could be key mediators in this interaction, regulating gene expression and the synthesis of inflammatory molecules. The objective of this systematic review was to evaluate the relationship between periodontitis and cardiovascular diseases by analyzing the expression of miRNAs involved in both pathologies.</p><p><strong>Methods: </strong>A systematic search was performed in the PubMed, Scopus, Embase, and Web of Science databases following the PRISMA guidelines. A total of 320 studies were identified, of which seven were included after applying eligibility criteria. Data on study design, sample characteristics, periodontal and cardiovascular diagnostic methodology, and the analyzed miRNAs were extracted.</p><p><strong>Results: </strong>The included studies were observational case-control studies in humans (<i>n</i> = 5) and experimental studies in animal models (<i>n</i> = 3). The miRNAs selected by the studies to link both pathologies were miR-155, miR-155-5p, miR-146a, miR-143, miR-145, and miR-23b. Most studies observed the overexpression of these miRNAs in patients with periodontitis and cardiovascular disease, with miR-146a being the most frequently associated.</p><p><strong>Conclusions: </strong>The findings suggest that certain miRNAs, particularly miR-146a, may play a key role in the connection between periodontitis and cardiovascular disease. Its overexpression in patients with both pathologies reinforces the hypothesis of its involvement in the inflammatory processes associated with both conditions. It would be interesting to conduct studies to validate their clinical applicability as biomarkers of susceptibility to cardiovascular disease.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Non-Coding RNAPub Date : 2025-05-05DOI: 10.3390/ncrna11030036
Rajdeep Banerjee
{"title":"Tiny but Mighty: Small RNAs-The Micromanagers of Bacterial Survival, Virulence, and Host-Pathogen Interactions.","authors":"Rajdeep Banerjee","doi":"10.3390/ncrna11030036","DOIUrl":"10.3390/ncrna11030036","url":null,"abstract":"<p><p>Bacterial pathogens have evolved diverse strategies to infect hosts, evade immune responses, and establish successful infections. While the role of transcription factors in bacterial virulence is well documented, emerging evidence highlights the significant contribution of small regulatory RNAs (sRNAs) in bacterial pathogenesis. These sRNAs function as posttranscriptional regulators that fine-tune gene expression, enabling bacteria to adapt rapidly to challenging environments. This review explores the multifaceted roles of bacterial sRNAs in host-pathogen interactions. Firstly, it examines how sRNAs regulate pathogenicity by modulating the expression of key virulence factors, including fimbriae, toxins, and secretion systems, followed by discussing the role of sRNAs in bacterial stress response mechanisms that counteract host immune defenses, such as oxidative and envelope stress. Additionally, this review investigates the involvement of sRNAs in antibiotic resistance by regulating efflux pumps, biofilm formation, and membrane modifications, which contribute to multi-drug resistance phenotypes. Lastly, this review highlights how sRNAs contribute to intra- and interspecies communication through quorum sensing, thereby coordinating bacterial behavior in response to environmental cues. Understanding these regulatory networks governed by sRNAs is essential for the development of innovative antimicrobial strategies. This review highlights the growing significance of sRNAs in bacterial pathogenicity and explores their potential as therapeutic targets for the treatment of bacterial infections.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Non-Coding RNAPub Date : 2025-05-01DOI: 10.3390/ncrna11030035
Maria Jose Navarro-Cobos, Carolyn J Brown
{"title":"Human XIST: Origin and Divergence of a <i>cis</i>-Acting Silencing RNA.","authors":"Maria Jose Navarro-Cobos, Carolyn J Brown","doi":"10.3390/ncrna11030035","DOIUrl":"10.3390/ncrna11030035","url":null,"abstract":"<p><p>Dimorphism of sex chromosomes often leads to a need for dosage compensation. In eutherian mammals, XIST, a long non-coding RNA, is expressed from the X chromosome that will be silenced, triggering X-chromosome inactivation (XCI). XIST originated from the ancestral protein-coding <i>Lnx3</i> gene with contributions from various mobile elements that contributed to the striking domains of tandem repeats within the first and sixth exons. Modular domains of XIST are now involved in recruiting heterochromatic marks and proteins essential for XCI initiation and maintenance. This review presents a comparative analysis of human <i>XIST</i> with five other eutherian mammals-chimpanzees, cats, pigs, sheep, and mice-examining conservation across exons as well as the tandem repeats. Notably, repeats exhibited higher conservation than exons, underscoring their functional importance. Additionally, a species-specific G repeat, previously described in pigs, was also identified in sheep and cats. These findings provide insights into the domains of XIST, a <i>cis</i>-acting silencer that has been used to proposed to alleviate the impact of a supernumerary chromosome in Down syndrome.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Building a Hand-Curated ceRNET for Endometrial Cancer, Striving for Clinical as Well as Medicolegal Soundness: A Systematic Review.","authors":"Roberto Piergentili, Stefano Sechi, Lina De Paola, Simona Zaami, Enrico Marinelli","doi":"10.3390/ncrna11030034","DOIUrl":"10.3390/ncrna11030034","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Competing endogenous RNAs (ceRNA) are molecules that compete for the binding to a microRNA (miR). Usually, there are two ceRNA, one of which is a protein-coding RNA (mRNA), with the other being a long non-coding RNA (lncRNA). The miR role is to inhibit mRNA expression, either promoting its degradation or impairing its translation. The lncRNA can \"sponge\" the miR, thus impeding its inhibitory action on the mRNA. In their easier configuration, these three molecules constitute a regulatory axis for protein expression. However, each RNA can interact with multiple targets, creating branched and intersected axes that, all together, constitute what is known as a competing endogenous RNA network (ceRNET). <b>Methods:</b> In this systematic review, we collected all available data from PubMed about experimentally verified (by luciferase assay) regulatory axes in endometrial cancer (EC), excluding works not using this test; <b>Results:</b> This search allowed the selection of 172 bibliographic sources, and manually building a series of ceRNETs of variable complexity showed the known axes and the deduced intersections. The main limitation of this search is the highly stringent selection criteria, possibly leading to an underestimation of the complexity of the networks identified. However, this work allows us not only to hypothesize possible gap fillings but also to set the basis to instruct artificial intelligence, using adequate prompts, to expand the EC ceRNET by comparing it with ceRNETs of other cancers. Moreover, these networks can be used to inform and guide research toward specific, though still unidentified, axes in EC, to complete parts of the network that are only partially described, or even to integrate low complexity subnetworks into larger more complex ones. Filling the gaps among the existing EC ceRNET will allow physicians to hypothesize new therapeutic strategies that may either potentiate or substitute existing ones. <b>Conclusions:</b> These ceRNETs allow us to easily visualize long-distance interactions, thus helping to select the best treatment, depending on the molecular profile of each patient, for personalized medicine. This would yield higher efficiency rates and lower toxicity levels, both of which are extremely relevant factors not only for patients' wellbeing, but also for the legal, regulatory, and ethical aspects of miR-based innovative treatments and personalized medicine as a whole. This systematic review has been registered in PROSPERO (ID: PROSPERO 2025 CRD420251035222).</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Non-Coding RNAPub Date : 2025-04-29DOI: 10.3390/ncrna11030030
Lea Sleiman, Sorina Dinescu
{"title":"Role of Non-Coding RNAs in White and Brown Adipose Tissue Differentiation and Development.","authors":"Lea Sleiman, Sorina Dinescu","doi":"10.3390/ncrna11030030","DOIUrl":"10.3390/ncrna11030030","url":null,"abstract":"<p><p>Adipocyte differentiation is a complex process in which pluripotent mesenchymal stem cells (MSCs) differentiate and develop into mature fat cells, also known as adipocytes. This process is controlled by various transcription factors, hormones, and signaling molecules that regulate the development of these cells. Recently, an increasing number of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), have been established to be involved in the regulation of many biological processes, including adipocyte differentiation, development, metabolism, and energy homeostasis of white and brown adipose tissue. Several in vitro and in vivo studies reported the significant role of ncRNAs in either promoting or inhibiting adipocyte differentiation into white or brown fat cells by targeting specific transcription factors and regulating the expression of key adipogenic genes. Identifying the function of ncRNAs and their subsequent targets contributes to our understanding of how these molecules can be used as potential biomarkers and tools for therapies against obesity, diabetes, and other diseases related to obesity. This could also contribute to advancements in tissue-engineering based treatments. In this review, we intended to present an up-to-date comprehensive literature overview of the role of ncRNAs, including miRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), focusing particularly on miRNAs, in regulating the differentiation and development of cells into white and brown adipose tissue. In addition, we further discuss the potential use of these molecules as biomarkers for the development of novel therapeutic strategies for future personalized treatment options for patients.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Non-Coding RNAPub Date : 2025-04-29DOI: 10.3390/ncrna11030033
Valeria Pecci, Melissa Borsa, Aurora Aiello, Sara De Martino, Luca Cis, Cristian Ripoli, Dante Rotili, Francesco Pierconti, Francesco Pinto, Claudio Grassi, Carlo Gaetano, Antonella Farsetti, Simona Nanni
{"title":"Bromodomain and Extra-Terminal Family Proteins BRD2, BRD3, and BRD4 Contribute to H19-Dependent Transcriptional Regulation of Cell Adhesion Molecules, Modulating Metastatic Dissemination Program in Prostate Cancer.","authors":"Valeria Pecci, Melissa Borsa, Aurora Aiello, Sara De Martino, Luca Cis, Cristian Ripoli, Dante Rotili, Francesco Pierconti, Francesco Pinto, Claudio Grassi, Carlo Gaetano, Antonella Farsetti, Simona Nanni","doi":"10.3390/ncrna11030033","DOIUrl":"10.3390/ncrna11030033","url":null,"abstract":"<p><strong>Background/objectives: </strong>Metastatic prostate cancer (PCa) remains a major clinical challenge with limited therapeutic options. The long non-coding RNA <i>H19</i> has been implicated in regulating cell adhesion molecules and collective migration, key features of metastatic dissemination. This study investigates the role of the Bromodomain and Extra-Terminal (BET) proteins BRD2, BRD3, and BRD4 in the <i>H19</i>-dependent transcriptional regulation of cell adhesion molecules. Currently, the major effects of BET inhibitors require androgen receptor (AR) expression.</p><p><strong>Methods: </strong><i>H19</i> was stably silenced in PC-3 (AR-null) and 22Rv1 (AR-positive) castration-resistant PCa cells. The cells were treated with the pan-BET inhibitors JQ1 and OTX015 or the BET degrader dBET6. In vivo, the effects of JQ1 were evaluated in xenograft mouse models. Chromatin immunoprecipitation (ChIP) and RNA-ChIP were used to assess BET protein recruitment and interaction with cell adhesion gene loci and <i>H19</i>. Organotypic slice cultures (OSCs) from fresh PCa surgical specimens were used as ex vivo models to validate transcriptional changes and BRD4 recruitment.</p><p><strong>Results: </strong>BET inhibition significantly reduced the expression of β4 integrin and E-cadherin and cell proliferation in both basal conditions, and following <i>H19</i> knockdown in PC-3 and 22Rv1 cells. These effects were mirrored in JQ1-treated tumor xenografts, which showed marker downregulation and tumor regression. ChIP assays revealed that BRD4, more than BRD2/3, was enriched on β4 integrin and E-cadherin promoters, especially in regions marked by H3K27ac. <i>H19</i> silencing markedly enhanced BRD4 promoter occupancy. RNA-ChIP confirmed a specific interaction between BRD4 and <i>H19</i>. These findings were validated in OSCs, reinforcing their clinical relevance.</p><p><strong>Conclusions: </strong>Our study demonstrates that BRD4 epigenetically regulates the <i>H19</i>-mediated transcriptional control of adhesion molecules involved in collective migration and metastatic dissemination. Importantly, these effects are independent of AR status, suggesting that targeting the <i>H19</i>/BRD4 axis may represent a promising therapeutic avenue for advanced PCa.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of Long Non-Coding RNA X-Inactive-Specific Transcript (<i>XIST</i>) in Neuroinflammation and Myelination: Insights from Cerebral Organoids and Implications for Multiple Sclerosis.","authors":"Nihan Aktas Pepe, Busra Acar, Gozde Erturk Zararsiz, Serife Ayaz Guner, Alaattin Sen","doi":"10.3390/ncrna11030031","DOIUrl":"10.3390/ncrna11030031","url":null,"abstract":"<p><p><b>Background/Objectives</b>: X-inactive-specific transcript (<i>XIST</i>) is a factor that plays a role in neuroinflammation. This study investigated the role of <i>XIST</i> in neuronal development, neuroinflammation, myelination, and therapeutic responses within cerebral organoids in the context of Multiple Sclerosis (MS) pathogenesis. <b>Methods</b>: Human cerebral organoids with oligodendrocytes were produced from <i>XIST</i>-silenced H9 cells, and the mature organoids were subsequently treated with either FTY720 or DMF. Gene expression related to inflammation and myelination was subsequently analyzed via qRT-PCR. Immunofluorescence staining was used to assess the expression of proteins related to inflammation, myelination, and neuronal differentiation. Alpha-synuclein protein levels were also checked via ELISA. Finally, transcriptome analysis was conducted on the organoid samples. <b>Results</b>: <i>XIST</i>-silenced organoids presented a 2-fold increase in the expression of neuronal stem cells, excitatory neurons, microglia, and mature oligodendrocyte markers. In addition, <i>XIST</i> silencing increased IL-10 mRNA expression by 2-fold and MBP and PLP1 expression by 2.3- and 0.6-fold, respectively. Although <i>XIST</i> silencing tripled IBA1 protein expression, it did not affect organoid MBP expression. FTY720, but not DMF, distinguished MBP and IBA1 expression in <i>XIST</i>-silenced organoids. Furthermore, <i>XIST</i> silencing reduced the concentration of alpha-synuclein from 300 to 100 pg/mL, confirming its anti-inflammatory role. Transcriptomic and gene enrichment analyses revealed that the differentially expressed genes are involved in neural development and immune processes, suggesting the role of <i>XIST</i> in neuroinflammation. The silencing of XIST modified the expression of genes associated with inflammation, myelination, and neuronal growth in cerebral organoids, indicating a potential involvement in the pathogenesis of MS. <b>Conclusions</b>: <i>XIST</i> may contribute to the MS pathogenesis as well as neuroinflammatory diseases such as and Alzheimer's and Parkinson's diseases and may be a promising therapeutic target.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}